In 1999, 3,924 women age 75+ years who were categorized as users (N=1944) or non-users (N=1980) of hormone replacement therapy (estrogen alone--ERT; estrogen plus progestin--HRT) based on computer-stored prescription data were recruited to a study of the prevalence and incidence of dementia in relation to ERT/HRT use. At recruitment, cognitive status and dementia (all dementia and probable Alzheimer's Disease--AD) were assessed using the modified Telephone Interview of Cognitive Status (TICSm), the Telephone Dementia Questionnaire (TDQ) and medical record review. ApoE genotype was determined for the 2,044 women who gave blood and consented to testing. The prevalence of cognitive impairment and dementia in relation to ERT/HRT use was assessed, and the results of this analysis were published. Non-demented women who completed the TICSm at baseline have been followed annually in order to ascertain incident cases of dementia and to track changes in cognitive status based on the TICSm. To date, we have completed 2 of 4 planned years of follow-up; 182 incident cases of dementia have been identified. The study still lacks power to assess dementia in subgroups of importance. The period of follow-up to assess changes in cognitive functioning is so far short. Thus, we propose to continue follow-up of women in the cohort for an additional four years. The primary aims of continuation of the cohort study are: 1) to increase the power of the study to assess dementia and probable AD in relation to ERT/HRT use; 2) to increase the power of the study to examine dementia and probable AD risk in relation to ERT/HRT in specific subgroups; and 3) to assess rates of cognitive decline in ERT/HRT users overall and in subgroups. The study will also maintain its bank of DNA and pursue promising genetic leads in dementia and late-onset AD, although there are no specific plans to conduct additional gene tests proposed now.